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Genetic elements regulating HES-1 induction in Wnt-1-transformed PC12 cells
1Howard Hughes Medical Institute, Department of Biochemistry and Kaplan Cancer Center, New York University Medical Center, New York 10016, USA.
Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
|October 28, 1998
Summary
Wnt-1 transformation increases HES-1 expression in PC12 cells by enhancing promoter activity. Transcription factor RBP-J kappa binding sites and novel elements contribute to this Wnt-1-induced HES-1 upregulation, impacting neuronal differentiation.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- PC12 cells normally differentiate into sympathetic neurons upon nerve growth factor (NGF) stimulation.
- Wnt-1 is crucial for mammalian brain development and its aberrant expression can disrupt neuronal differentiation.
- Previous work indicated elevated HES-1, a neuronal differentiation inhibitor, in Wnt-1-transformed PC12 cells.
Purpose of the Study:
- To investigate the regulatory mechanisms underlying increased HES-1 expression in Wnt-1-transformed PC12 cells.
- To identify specific DNA elements and transcription factors responsible for Wnt-1-mediated HES-1 promoter activation.
Main Methods:
- Utilized Wnt-1-transformed PC12 cells and parental PC12 cells.
- Performed promoter activity assays to compare HES-1 promoter function.
- Analyzed the role of RBP-J kappa binding sites in HES-1 promoter induction.
- Identified and characterized novel Wnt-1-responsive promoter elements through protein-DNA binding studies.
Main Results:
- Wnt-1 transformation significantly increased HES-1 promoter activity in PC12 cells.
- Binding sites for transcription factor RBP-J kappa were found to be critical for this promoter induction.
- Two additional novel promoter elements were identified that are essential for elevated HES-1 expression.
- One novel element specifically binds Wnt-1-induced protein complexes.
Conclusions:
- Wnt-1 signaling upregulates HES-1 expression in PC12 cells through enhanced promoter activity.
- RBP-J kappa and novel Wnt-1-responsive elements mediate this transcriptional regulation.
- Understanding these Wnt-1 pathways provides insights into nuclear signaling regulating neuronal differentiation.